This application addresses broad Challenge Area (05) Comparative Effectiveness Research, and specific Challenge Topic 05-AI-102: Comparative-effectiveness of Anti Retroviral Therapy (ART). We propose to assess the comparative effectiveness of ART in two specific patient populations of widespread importance: older HIV-infected individuals with cardiovascular risk factors or established cardiovascular disease, and HIV- infected patients with multi-drug resistant virus. We respond to the American Recovery and Reinvestment Act of 2009 by proposing a project which is ready for execution, will be completed within 2 years, will lead directly to the creation of 2 new jobs (programmer and research assistant) and the retention of 2 additional jobs (Bendavid, Sundaram). The project can begin immediately because the data on which we will perform our analyses is currently available. We have unique data sources that will enable us to address these questions more definitively than has been possible previously. We have assembled a multi-disciplinary team of highly experienced investigators with extensive expertise in comparative effectiveness, cost effectiveness, clinical care of HIV disease, statistics, health economics, and mathematical modeling. Our analyses will provide important information for clinicians, patients, and policymakers on the comparative effectiveness of treatments for individuals with HIV. This study has 2 aims. 1. To evaluate the comparative effectiveness and cost effectiveness of treatment for older HIV-positive individuals with cardiovascular risk factors or established cardiovascular disease. We will use the Department of Veterans Affairs (VA) HIV Clinical Case Registry (CCR) of more than 55,000 HIV patients to assess whether exposure to specific antiretroviral drugs or regimens is associated with poorer outcomes in patients with cardiovascular risk or disease. We will develop a decision model to evaluate long-term health and economic outcomes of different regimens. 2. To evaluate the comparative effectiveness and cost effectiveness of the use of new antiretrovirals - including but not limited to second generation protease inhibitors, integrase inhibitors, and entry inhibitors - in treatment-experienced HIV-infected individuals with multi-drug resistant virus. The project will aim to improve treatment choices for individuals with HIV by improving ART choice selection in patients with co-morbid disease or with multi-drug resistant HIV. The project will aid both in creation of new positions and retention of existing positions. PUBLIC HEALTH RELEVANCE: This application addresses broad Challenge Area (05) Comparative Effectiveness Research, and specific Challenge Topic 05-AI-102: Comparative-effectiveness of Anti Retroviral Therapy (ART). The project will compare antiretroviral strategies in HIV-infected individuals with cardiovascular risk factors or cardiovascular disease, and in patients with multi-drug resistant HIV. The project will enhance knowledge about the relationship between exposure to antiretroviral therapy and health outcomes, and improve decisions about choice of ART in individuals with cardiovascular risk factors and with multi-drug resistant infection.